Investigation of carbohydrate metabolism and somatomedin in osteosarcoma patients. Altered carbohydrate metabolism associated with fibrosarcomas and chondrosarcomas has been well-documented in past literature. This report describes abnormal carbohydrate metabolism in 2 osteosarcoma patients, and abnormalities in growth hormone and somatomedin serum levels. Experimental evidence is presented showing in vitro suppression of osteosarcoma tumor cell proliferation by 17 beta Estradiol. Estrogen inhibition of linear bone growth, cartilage proliferation, and somatomedin is discussed with reference to possible estrogen therapy in osteosarcoma.


The platelets in preleukemia and myelomonocytic leukemia. Ultrastructural cytochemistry and cytogenetics. Light and electron microscopic studies of platelets from 16 patients with myelomonocytic leukemia or "preleukemia" revealed major morphologic alterations in 15 and minor ones in 1. Although variable in severity from case to case, the changes present followed a distinct pattern. In most cases there were two platelet populations, one morphologically normal and one morpholigically abnormal. The most salient changes pertained to size (giant forms), shape (the platelets being rounded and probably spheroidal), decrease or absence of the microtubules, and increase in immature elements. A striking feature was the variation in size and shape of the granules, with truly giant forms (up to 2.5 mum) being present. In cytogenetic studies in 14 cases, there was no correlation between the chromosomal changes and the various types of platelet anomalies.


Unusual orbital tumors and their treatment.


The university and the community.

The university and the community.


Presence of antibody to a primate RNA virus in human plasma.


Hairy cell leukemia - reclassification of an old entity.


Prophylactic antibodies in hysterectomy.


Editorial: An improved health service.

Editorial: An improved health service.


Early experience with total knee replacement. This paper presents a review of two years' experience with the geometric total knee replacement. The results of 23 arthroplasties in 22 patients are discussed. Relief of pain was consistent and dramatic, movement was increased postoperatively in only three patients, but imporvement in overall function occurred in 20 of the 22 patients. There was one failure requiring arthrodesis. In this patient, six months after surgery the medial tibial condyle collapsed and the polyethylene tibial component fractured. This complication has not been reported before. Early results are encouraging. Total knee joint replacement is a useful procedure in advanced arthritis when arthrodesis is the only alternative.


Letter: Practolol reaction.

Letter: Practolol reaction.


Chronic granulomatous disease: an inherited disorder of phagocytosis in a Maori ancestry. Chronic granulomatous disease, in which abnormal susceptibility to infection is caused by an inherited defect in phagocytic cells, has been diagnosed in three brothers. Two brothers had repeated bacterial infections of the skin, superficial lymph nodes and lungs from infancy and died aged 27 months and 13 months. Characteristic suppurating granulomata were found in many organs. The diagnosis was established in both during life, and in the third asymptomatic brother shortly after birth, by studies of phagocytic function which included tests for nitroblue-tetrazolium reduction, hexose monophosphate shunt activity and bactericidal capacity. Their mother and a maternal aunt, both Maoris with no known Caucasian ancestry, were identified as carriers of the presumed sex-linked recessive gene. The clinical features of the disease and the laboratory methods for diagnosis are described.


Medical services at a music festival.

Medical services at a music festival. A three-day open air musical festival attended by approximately 20 000 people was held at Ngaruawahia in January 1973. A medical service was provided and staffed mainly by medical students, nurses and young medical graduates. There were 1998 patient visits to the medical area, the five most common complaints being sunburn, headaches, minor foot trauma, gastroenteritis and lacerations which collectively accounted for 75 percent of the diagnoses. The medical services provided are discussed and recommendations for future festivals made.


Smoking behaviour and respiratory health in teenage sample: the rotorua lakes study, 1. A survey in a New Zealand high school compared boys and girls, Maori and European, aged 13 to 15 years, and found differences in smoking habits. Smoking was most prevalent in Maori students of both sexes, and least in European girls, who appeared to be most influenced by home factors such as father's occupational status and older siblings' habits. Maori students and European boys showed relationships rather to the habits of the peer group. Findings were comparable with earlier studies suggesting little secular change in the smoking habits of this age group. Current smokers in all sex/race groups had higher current respiratory morbidity scores than non-smokers and ex-smokers, and smoking partly accounted for racial differences in morbidity.


Youthline Dunedin: an evaluation of a telephone counselling service. Youth Dunedin is a telephone counselling service which has been in operation for over two years. The type and pattern of calls is discussed, and results of a survey aimed at eliciting how well the youth of Dunedin know of the operations are presented. The trend in the number of calls is forecast. The calls over a wide range of concerns with no noted daily or monthly pattern. There is an upward trend in the frequency of calls.


Performance of the Dalkon Shield intrauterine device. A modern second generation intrauterine device, the Dalkon Shield has been assessed at the National Women's Hospital. The markedly low expulsion rate represents a real advance in intrauterine contraception. Pregnancy rates are comparable with other modern devices. Patient acceptability is higher than with earlier devices.


Letter: Overcoming the doctor shortage: some practical suggestions.


Solo mothers after delivery at Christchurch. A questionnaire was sent to 130 single mothers who kept their infants after delivery. The questionnaire was designed to find out the needs if any, of solo mothers. The Social Welfares Services were not fully utilised.


Letter: Urinary antiseptics in asymptomatic bacteriuria of pregnancy.


Flicker fusion threshold in mental illness.


Chiropractic: not an alternative system of primary health care.


An epizootic of malignant catarrhal fever. 2. Laboratory investigations.


The value of plasma fibrinogen estimations in cattle: a comparison with total leucocyte and neutrophil counts.


Deer farming in New Zealand.

Deer farming in New Zealand.


The Salmonella excretor incidence of dogs in Hawke's Bay.


Facial eczema: zinc responsiveness in dairy cattle.


Osteochondritis in a thoroughbred foal.

Osteochondritis in a thoroughbred foal.


Letter: Toxoplasma encephalitis in a cat.


Letter: New parasite records from the South Island.


The effects of copper supplementation on stock health and production. I. Field investigations into the effects of copper supplementation on stock health in dairy herds with a history of post-parturient haemoglobinuria.


Milk production increases following treatment of subclinical parasitisms in Wisconsin dairy cattle.


Caeruloplasmin activity as an indication of plasma copper levels in sheep.


Letter: Petriellidium boydii from the reproductive tracts of mares.


Letter: Mycoplasmosis in poultry.

Letter: Mycoplasmosis in poultry.


Control of ovine posthitis in merinos grazing improved pastures in the South Island high country.


The anthelmintic efficacy of mebendazole against adult Fasciola hepatica and a concurrent mixed nematode infection in sheep.


The anoestrous syndrome in new zealand dairy cattle. 2. Some factors influencing submission rates in Taranaki herds.


An epizootic of malignant catarrhal fever. 1. Clinical and pathological observations.


Electric shocks during machine milking.

Electric shocks during machine milking.


Letter: A coronavirus-like agent present in faeces of cows with diarrhoea.


Calcinosis circumscripta-like lesions in dogs associated with the use of choke chains.


The effects of copper supplementation on stock health and production. 2. The effect of parenteral copper on incidence of disease, haematological changes and blood copper levels in a dairy herd with hypocuprosis.


Behaviour of early-weaned calves in indoor individual cubicles and group pens.


Letter: Population changes of the itch mite, Psorergates ovis, after shearing.


The bacterial flora of the respiratory tract of normal and pneumonic sheep.


The identity and occurrence of coccidia species in some New Zealand pigs.


Treatment of Taenia hydatigena infections in dogs with bunamidine hydroxynaphthoate incorporated in food.


The prevalence of Mycoplasma ovipneumoniae and Mycoplasma arginini in the respiratory tract of sheep.


Bilateral asymmetry of equine laryngeal muscles.


Fatal ancylostomiasis in a dog.

Fatal ancylostomiasis in a dog.


A case of equine laryngospasm.

A case of equine laryngospasm.


Letter: Poisoning of cattle by Amaranthus.


Letter: Serological evidence for infection of sheep with Leptospira interrogans serotype hardjo.


Letter: Constant replenishment of sheep dips.


Editorial: What do I get for my dental society dues?


Letter: Chicken mite (Dermanyssus gallines) infesting a dog.


Dentists' reaction to a new preventive agent.


Editorials: Clear and present danger.

Editorials: Clear and present danger.


Letter: An exchange of opinion.

Letter: An exchange of opinion.


Importance of dental x-rays.

Importance of dental x-rays.


Editorial: Conspicuous waste.

Editorial: Conspicuous waste.


Orthodontic evaluation.

Orthodontic evaluation.


Women dental students.

Women dental students.


Kinematics in TMJ problems. Three-case report.


How the aging process affects dental pulp.


Editorial: Protecting the dental turf is not enough.


Editorial: Acupuncture: from then to now.


A symposium on the British Health System. A report.


Viral hepatitis: its importance to dentists.


Odontophilately.

Odontophilately.


Pancytopenia: a case for pretreatment hematologic investigation.


The role of odontoplasty in preventive and orthodontic procedures.


The dental management of patients with medical problems.


Copying x-rays.

Copying x-rays.


Editorial: Augmented auxiliaries--an embarrassment of riches?


Letter: Impressions of a young member.

Letter: Impressions of a young member.


Nursing home codes as they relate to dentistry.


Editorial: An answer to compulsory continuing education. The greater N.Y. dental meeting.


Third man out: a possible alternative to "dental insurance.'.


Barefoot dentists.

Barefoot dentists.


Fractured tooth--a case report.

Fractured tooth--a case report.


Patient fears: sources and sauces.

Patient fears: sources and sauces.


Letter: Insurance coverage after age 70.


Letter: Interstitial air emphysema cases.


Prepaid dental plans.

Prepaid dental plans.


Frequency of hepatitis in dentists in Ontario.


Pediatric mandibular fractures.

Pediatric mandibular fractures. This article is a study of the experience with mandibular fractures at a large pediatric hospital. A total of ninety-four mandibular fractures in sixty-three patients is reviewed. The cause, location, male-female ratio, occurrence of multiple fractures, and associated problems are studied.


Comparison of two submandibular incisions on the motor function of the lower lip. The usual submandibular surgical approach to the mandible carries with it the risk of injury to the mandibular ramus of the seventh nerve. This may result in transient or permanent palsy of the lip. In a study of twenty operative procedures, of which half were performed at the conventional level and the other half at a lower level, an interesting contrast in facial nerve involvement was noted: 50 per cent at the conventional incision and none at the inferior one.


The styloid or "Eagle" syndrome: an unexpected consequence. The development and pathogenesis of the elongated styloid process with a calcified stylohyoid ligament are reviewed and discussed. A case report is presented to demonstrate that, although the related symptoms may be mild, unless the patient is aware of the cause of the discomfort, a "cancerophobia" may cause great emotional distress.


Immediate repair of gingival biopsy sites.


Mandibular distomolars. A review of the Japanese literature and a report of three additional cases.


Primordial cyst versus keratocyst.

Primordial cyst versus keratocyst. The term primordial cyst was introduced in 1945 to identify the odontogenic cyst formed from enamel organ before calcification occurred as part of a classification based on development, structure, and radiographic appearance. The term odontogenic keratocyst was introduced in 1956 to describe cysts of the jaw exhibiting keratinization of their lining. Periodontal, dentigerous, primordial, residual, and gingival cysts may exhibit keratinized linings and can properly be identified as odontogenic keratocysts on the basis of their histologic appearance but may also be identified by their "developmental" designation. There is no justification for considering odontogenic keratocyst as a synonym for primordial cyst.


The effect of steroid hormones on buccal mucosa of menopausal women. The effects of local application of estrone and progesterone on the oral mucosa was studied in sixty-one patients. These included forty-one postmenopausal women with various subjective oral complaints, ten postmenopausal women with no oral complaints, and ten normally menstruating women. Subjective complaints (dryness, bad taste, burning sensation, and viscous saliva), quantity of saliva, and histologic changes in buccal mucosa were evaluated before and after treatment. Treatment comprised three modalities: an ointment containing estrone alone; another ointment of estrone and progesterone; and a third with a placebo base. These were massaged three times daily over the gingivae and oral mucosa for 30 days. A significant increase in secretion of saliva was observed with all three treatment modalities. Biopsies showed marked proliferative changes with all three types of ointment. A moderate improvement in subjective complaints followed all types of medication. These results indicate no specific effect of female sex hormones on the factors considered in this study. It appears that simple, repeated massage with any suitable ointment base is an effective method of inducing proliferative changes in atrophic buccal mucosa, increasing salivary secretion, and alleviating some of the subjective oral complaints of postmenopausal women.


An evaluation of the rinse technique for oral cytologic diagnosis.


The C.C.A. syndrome (congenital contractural arachnodactyly): a new differential syndrome for Marfan's syndrome and homocystinuria. The first case in the dental literature of congenital contractural arachnodactyly (C.C.A. syndrome) is presented. This newly delineated syndrome is an autosomal dominant heritable disorder of connective tissue. Its similarities to Marfan's syndrome and homocystinuria, as well as other syndromes, are discussed. The lack of cardiovascular disease, specific ocular anomalies, and mental retardation are presented in the differential diagnosis of the C.C.A syndrome with Marfan's syndrome and homocystinuria.


Oral nodular excrescences in epidermolysis bullosa. Two brothers are reported with what appears to be a recessive and dystrophic type of epidermolysis bullosa. The oral lesions seen in these patients consisted of small fibrous nodules that were liberally distributed on the bound-down mucosa. These lesions have not been previously reported. One of the offspring of these patients, who was not affected by epidermolysis bullosa, was missing a large number of teeth.


Mucoepidermoid carcinoma arising within a Warthin's tumor. A case of low-grade mucoepidermoid carcinoma arising within a Warthin's tumor is reported. The carcinoma appeared to have originated from the hyperplastic atypical epithelium of the Warthin's tumor. It did not infiltrate the capsule of the lymph node in which the Warthin's tumor developed. After 6 years of follow-up, there is no evidence of recurrence or metastasis. The literature on malignant Warthin's tumor is reviewed.


Nodular fasciitis.

Nodular fasciitis. The case of a highly unusual lesion present in the mandibular area is reported. Operative intervention was successful, and healing was uneventful. The pathologic diagnosis was difficult to make because of the nature of the lesion.


Seminoma metastatic to the jaws. Report of a case.


Felty's syndrome.

Felty's syndrome. The clinical and pathologic findings of Felty's syndrome are discussed. A case is presented which demonstrates the nonspecific inflammatory oral lesions commonly seen with this syndrome. The role of the dentist in relating these nonspecific lesions to the basic disease process is emphasized.


Automatic processing of intraoral films in dental schools. Most of the active and provisional members of the American Association of Dental Schools used automatic processors for developing, fixing, and washing intraoral x-ray films. The S. S. White Auveloper was the processor most commonly used, the next most common being Litton's Profexray. Processing solutions were changed, on the average, two to three times a month. The quality of developing, fixing, and washing was generally reported to be satisfactory. The one major drawback to automatic processing was breakdown and malfunction of equipment.


Variations in the interpretation of periapical radiolucencies. Comparison of the first and second interpretations by means of measurements on enlarged tracings of forty-five periapical radiolucencies by ten experienced dentists revealed an average relative error of interpretation of 21 per cent for the area measurements of the readily defined radiolucencies and 37 per cent for the area measurements of the diffuse radiolucencies. Comparing the dentists, the relative error of interpretation by means of measurements of the area varied from 14 to 32 per cent for the readily defined radiolucencies and from 23 to 52 per cent for the diffuse radiolucencies. The differences in interpretation were more obvious in the area measurements than in the measurements of the largest distance between the root surface and the outline of the radiolucency or the largest diameter.


Inverted mandibular premolar.

Inverted mandibular premolar.


Bilateral multiple mandibular tori.

Bilateral multiple mandibular tori.


Fibro-osseous lesion of the mandible mimicking chronic osteomyelitis. An account is given of the clinical, radiologic, and pathologic, features of a special form of fibro-osseous lesion of the mandible. The material consists of fifteen cases (eleven females and four males). Two cases are described in detail. Together with Case 1, a probably unique series of radiographic pictures is presented, showing the development of the disease.


Comment on reactive hyperplasia of bone.


Ameloblastoma of the jaws in Nigerian children. A review of sixteen cases. The records of sixteen patients under 18 years of age with ameloblastoma of the jaws treated at the University College Hospital, Ibadan, Nigeria, within the last 10 years were examined. In fifteen of the sixteen cases, the tumor was found in the mandible, with the symphysis being affected in seven cases. The ease with which the monocystic type of the tumor may be confused with a dentigerous cyst is pointed out. The different methods of treatment of ameloblastoma of the jaws in children are discussed.


The disturbances in odontogenesis in epidermolysis bullosa hereditaria letalis. The disturbances in odontogenesis in a case of epidermolysis bullosa hereditaria letalis are described, with particular emphasis on the morphologic alterations in the ameloblasts and on the nature of vesicles in the enamel organ. These latter structures are compared to those found in the skin.


Scanning and transmission electron microscopy of odontogenic keratocysts. The ultrastructural characteristics of the superficial cells of the epithelial lining of odontogenic keratocysts were studied. Examples of both the parakeratinized type and the less common orthokeratinized variant were examined. Scanning electron microscopy reveals that the morphology of the two cyst types is distinctly different. In parakeratinized cysts the transition of the epithelial cells into parakeratin is readily apparent and the epithelial surface is sparsely covered with parakeratin squames. In the orthokeratinized type the surface morphology is more uniform and is entirely covered with a leafy layer of keratin squames. The morphologic differences between the parakeratinized and orthokeratinized cysts may reflect differences in their biologic behavior.


Craniometaphyseal dysplasia. Report of a case. Craniometaphyseal dysplasia, often referred to as Pyle's disease, is a hereditary disease involving the expansion of the metaphyses of the long bones, giving the appearance of an Erlenmeyer flask. There is diffuse hyperostosis of the entire cranial vault, along with absence or decreased development of the paranasal sinuses. In the case presented here the mouth demonstrated an abnormality wide maxilla with a slight palatal vault. Genetically, this appeared to be a dmoninant form of dysplasia.


Calcifying epithelial odontogenic tumor. A histologic, histochemical, fluorescent, and ultrastructural study. A previously unreported calcifying epithelial odontogenic tumor (CEOT; Pindborg tumor) occurring in a Negro patient is presented. Only 12 per cent of these neoplasms have been found in nonwhite patients. Ultrastructural and histochemical studies indicated that the amorphous, acellular, eosinophilic substance present within the tumor was not amyloid. The presence of only sparse calcifications is an unusual histologic variant. No relationship between neoplasm and reduced enamel epithelium could be demonstrated.


Odontogenic tumors in an African population. Analysis of twenty-nine cases seen over a 5-year period. The patients reported on here were seen and treated in the Department of Oral Surgery and Pathology, Division of Dentistry, Lagos University Teaching Hospital, between September, 1969, and September, 1974. Materials for histopathologic examination came from tissues removed at biopsy or surgical excision of the lesions. Out of a total of about 200 benign and malignant lesions of the oral cavity seen during the 5-year period (all cysts excluded), twenty-nine (15 per cent) were tumors arising from the odontogenic tissues as follows: ameloblastoma, nineteen; ameloblastic fibroma, two; adrenomatoid odontogenic tumor, two; ameloblastic fibro-odontoma, one; odontoma, two; cementoma, two; and calcifying odontogenic cyst, one. The author had the privilege of seeing all the patients and examining all the biopsy and surgical specimens.


Exposure factor determination.

Exposure factor determination. Differences in radiation output between dental x-ray generators operated with a given electrical input often discourage the practitioner from trying to use supplemental x-ray techniques. Methods are described by which the exposure time is easily computed for an generator, regardless of cone length, kilovoltage, milliamperage, or idiosyncrasies of output.


Endodontic emergency dilemma: leave tooth open or keep it closed? Various methods of emergency endodontic treatment for teeth with vital pulps have been suggested, and some authors have advised that the access be left open if the tooth is tender to percussion. This study evaluated 225 open and closed teeth which were referred after emergency treatment where pulps had been vital. When the access had been left open, a statistically significant greater number of appointments were needed to complete treatment and more intratreatment exacerbations occurred than when the tooth was kept sealed.


The diagnostic correlator: an endodontic teaching device. A chart is proposed as an aid to assist students and practitioners to correlate clinical information and arrive at an accurate endodontic diagnosis. A brief description of current displays, the clinical examination, and an endodontic disease classification is given. A discussion and examples of how to use the chart are presented. The chart has been found to be a useful teaching aid.


Four impacted fourth molars.

Four impacted fourth molars.


An alternative approach to dose reduction in dental radiography. A responsible approach to dose reduction in dental radiography requires that relative exposure be related to the specific diagnostic task performed. All but the most demanding tasks can be performed when suitable film is used in conjunction with high-speed screens. Placing the source of radiation inside the mouth permits radiographic information to be recorded on an improved Polaroid cassette that has a relatively high quantum efficiency. As a result, the radiation dose can be significantly reduced in a versatile system which provides for instantaneous processing and interpretation from prints rather than negatives.


The development of drug-resistant strains of Eimeria maxima in the laboratory. The development of strains of Eimeria maxima resistant to buquinolate, methyl benzoquate, clopidol, sulphaquinoxaline and robenidine is described. It was not possible to standardize a schedule of inoculations and drug administration, which would enable the development of resistance to the different drugs to be compared directly. Resistance developed most readily to the quinolones. One robenidine-resistant strain proved to be drug-dependent. Dinitolmide showed unusual effects upon sporogony and three attempts to develop resistance against this activity failed. Chicks previously immunized with the parent strain were completely protected against infection with the drug-resistant strains.


Coexistence of different pathologic entities.


Eimeria tenella in chickens: development of resistance to quinolone anticoccidial drugs. The development of drug resistance by the present Houghton strain of Eimeria tenella to the quinolones, methyl benzoquate and buquinolate, was found to take place after a single experimental passage. The development of resistance was independent of drug selection pressure and showed cross resistance to other quinolones, but not to amprolium and robenidine. When the Weybridge, Beltsville and Elberfeld strains of E. tenella were compared under similar laboratory conditions, the Weybridge and Elberfeld strains developed resistance to methyl benzoquate after 6 passages and the Beltsville after 5. Studies on the response of the Houghton strain to methyl benzoquate and buquinolate revealed that the drugs did not completely control the infection as measured by weight gain and that oocyst production was not suppressed. These observations indicate that the strain had already acquired some resistance to these drugs. This was confirmed by examining the resistance to methyl benzoquate of a culture of the Houghton strain of E. tenella which had been stored frozen in liquid nitrogen since 1969. This showed full sensitivity to the drug and developed resistance after 8 passages. This suggests that drug tolerance has been acquired by the Houghton strain since 1969. Oocyst lines were established from the Houghton strain by infecting single birds with approximately 10 oocysts. Eleven of these lines were found to be sensitive to methyl benzoquate, and nine to give rise to resistant parasites. It is concluded that the Houghton strain is contaminated by a small number of resistant oocysts which can be eliminated from a culture by dilution of the challenge inoculum. One of these Houghton oocyst lines, sensitive to methyl benzoquate, developed resistance after 8 serial passages.


Late familial pseudo-myopathic muscular glycogenosis with alpha 1,4 glucosidase deficiency. Morphological, histoenzymological and biochemical approach.


The negative-pressure respirator: an improved design.


Antigen mobility in membranes and complement-medical immune attack. The complement fixing activity of liposomes containing cholesterol, dimyristoylphosphatidylcholine (or dipalmitoylphosphatidylcholine), and 3 mol % of cardiolipin has been studied as a function of cholesterol concentration by use of human syphilitic serum containing cardiolipin-specific (Wasserman) antibodies. It is found that complement fixation increases rapidly for cholesterol concentrations above 35 mol %. Spin label studies have been used to study the incorporation of cardiolipin in the relatively rigid phase of binary mixtures of cholesterol and dimyristolphosphatidycholine (or dipalmitoylphosphatidylcholine). It is concluded that cardiolipin is included in such a phase of these lipids for cholesterol concentrations above 35 mol %. These results indicate that a relatively rigid lateral distribution of this monovalent antigen in the plane of the membrane facilitates complement fixation and concomitant complement-mediated membrane damage.


Attraction of the oriental fruit fly, Dacus dorsalis, to methyl eugenol and related olfactory stimulants. The attraction of male oriental fruit flies to methyl eugenol and 34 analogues was investigated quantitatively using the characteristic feeding response. Methyl eugenol was the most active compound studied, with a feeding response to 0.01 mug, but saturation of the allyl side chain or replacement of allyl by allyloxy produced compounds almost as effective. Replacement of the methoxy groups by methylenedioxy, methyl, or chloro groups abolished all response. The ring geometry of the methoxy groups was critical, with orthodimethoxy most active and meta-dimethoxy inactive. Replacement of methoxy with hydroxy, methylthio, or amino groups did not abolish the response. The failure of the oriental fruit fly to respond to the methyl and chloro isosteres of methyl eugenol was contrasted with the response of a human odor panel which perceived these compounds as having weak floral odors.


Preparation and microbial decomposition of synthetic [14C]ligins. A definitive assay for microbiological and biochemical research on the biodegradation of lignin was developed using radioactive synthetic lignins specifically labeled in the side chains, aromatic rings or in the methoxyl groups. The [14C]lignins were prepared by oxidative polymerization with peroxidase and H2O2 Of specifically labeled coniferyl alcohol (4-hydroxy-3-methyoxycinnamyl alcohol). The synthetic polymers were shown by spectroscopic and chemical methods to contain the same intermonomer linkages found in natural lignins. Incubation of the [14C]lignins with known lignin-degrading fungi and with a forest soil resulted in 14CO2 evolution.


Modification of the 5'-terminus of mRNA by soluble guanylyl and methyl transferases from vaccinia virus. RNA guanylyl and methyl transferases have been solubilized from vaccinia virus cores. The guanylyl transferase specifically adds a GMP residue to the 5'-terminus of unmethylated vaccinia virus mRNA to form the structures G(5')ppp(5')Gp- and G(5')ppp(5')Ap-. Studies with [alpha-32P]GTP and [beta, gamma-32P]GTP indicated that only the alpha-phosphate is transferred. In the presence of S-adenosylmethionine, the methyl transferases convert the blocked 5'-termini to m7G(5')ppp(5')Gmp- and m7G(5')ppp(5')Amp-. Similarly, the enzymes can modify synthetic poly(A) to form the structure m7G(5')ppp(5')Amp-.


Interaction of cholera toxin and membrane GM1 ganglioside of small intestine. Ganglioside GM1 was isolated from the small intestinal mucosa of man, pig, and beef and amounted to 0.1, 2.0, and 43 nmol per g fresh weight, respectively. These differences in GM1 content were associated with a quantitatively differing ability of the mucosal cells to bind cholera toxin. Human cells bound about 15,000 toxin molecules when saturated with the toxin, porcine cells 120,000, and bovine cells 2,600,000 molecules. The association constant (KA) of the cholera toxin binding was, for cells of all three species, about 10(9) liters/mol. Exogenously added GM1 ganglioside was incorporated in intestinal mucosal cells as well as in intact rabbit small bowel. The increment in GM1 was associated with a correspondingly increased number of binding sites for cholera toxin, whereas KA was unchanged. GM1 incorporation increased the sensitivity of the rabbit small bowel to the diarrheogenic action of cholera toxin. Vibrio cholerae sialidase hydrolyzed isolated intestinal diand trisialogangliosides to GM1. However, the enzyme did not change the ganglioside pattern of intestinal mucosa, had very little influence on the number of toxin binding sites on intestinal cells, and did not alter the sensitivity of the small bowel to the diarrheogenic action of the toxin. These results demonstrate a relationship in the intestinal mucosa between the GM1 ganglioside concentration, the number of binding sites for cholera toxin, and the sensitivity to the biologic action of the toxin. Thus, the study strongly supports the concept that the GM1 ganglioside is the intestinal binding receptor for cholera toxin.


Molecular orbital studies of enzyme activity: I: Charge relay system and tetrahedral intermediate in acylation of serine proteinases. The charge relay ststem and its role in the acylation of serine proteinases is studied using the partial retention of diatomic differential overlap (PRDDO) technique to perform approximate ab initio molecular orbital calculations on a model of the enzyme-substrate complex. The aspartate in the charge relay system is seen to act as the ultimate proton acceptor during the charging of the serine nucleophile. A projection of the potential energy surface is obtained in a subspace corresponding to this charge transfer and to the coupled motions of active site residues and the substrate. These results together with extended basis set results for cruder models suggest that a concerted transfer of protons from Ser-195 to His-57 and from His-57 to Asp-102 occurs with an energy barrier of 20-25 kcal/mole (84-105 kJ/mole). The subsequent nucleophilic attack on the scissile peptide linkage by the charged serine is then seen to proceed energetically downhill to the tetrahedral intermediate. The formation of the tetrahedral intermediate from the Michaelis complex is calculated to be nearly thermoneutral.


Cholera toxin activation of adenylate cyclase in cancer cell membrane fragments. Activation of adenylate [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by cholera toxin (84,000 daltons, 5.5 S) is demonstrated in plasma membrane fragments of mouse ascites cancer cells. The activation of adenylate cyclase is mediated by a macromolecular cyclase activating factor (MCAF), which has a sedimentation constant of 2.7 S and a molecular weight of about 26,000. MCAF is derived from, and may be identical to the "A fragment" of cholera toxin. Generation of MCAF depends on prior interaction of cholera toxin with either dithiothreitol, NADH, NAD, or a low-molecular-weight component (less than 700 daltons) present in cytoplasm. Subsequent exposure of this pretreated cholera toxin to cell membranes from a variety of mouse ascites cancer cells is followed rapidly by the appearance of MCAF, which no longer requires dithiothreitol, NADH, or NAD for the activation of adenylate cyclase. Activation of adenylate cyclase by MCAF in ascites cancer cell membrane fragments is not reversed by repeated washing of these membrane fragments. Adenylate cyclase in normal cell membrane fragments fails to respond either to cholera toxin or MCAF in the presence of dithiothreitol. In striking contrast, the adenylate cyclase in membrane fragments from five ascites cancer cells responds to either MCAF or native cholera toxin preincubated with dithiothreitol, NADH, or NAD.


Site-specific cleavage of single-stranded DNA by a Hemophilus restriction endonuclease. Single-stranded viral DNA of bacteriophage f1 is cleaved into specific fragments by endo R-HaeIII, a restriction endonuclease isolated from Hemophilus aegyptius. The sites of the single strand cleavage correspond to those of the double strand cleavage. A single-stranded DNA fragment containing only one HaeIII site is also cleaved by this enzyme. This observation suggests that the reaction of single-stranded DNA cleavage does not require the formation of a symmetrical double-stranded structure that would result from the intramolecular base-pairing between two different HaeIII sites. Other restriction endonucleases may also cleave single-stranded DNA.


Amino-acid sequence of activation cleavage site in plasminogen: homology with "pro" part of prothrombin. A 38-residue fragment is isolated from carboxymethylated plasminogen. Residues 29-38 have the same sequence as the amino-terminal end of the light chain of plasmin. The sequence 1-28 is therefore the sequence of the carboxyl-terminal end of the heavy chain and contains the specific sequence at which urokinase (EC 3.4.99.26) and other plasminogen-activating serine proteases split. Two of the five carboxymethyl-cysteine residues in the isolated fragment are situated close to the cleavage site and the fragment is not itself a substrate for plasminogen-activators. Residues 1-11 show extensive sequence homology with residues 137-147 and 242-252 in prothrombin, which are located in corresponding regions of the two internally homologous 83-residue structures in the non-thrombin part of the molecule, indicating that such structures may be a common feature of the non-protease part of the larger serine protease zymogens.


Minimal requirements for template recognition by bacteriophage Qbeta replicase: approach to general RNA-dependent RNA synthesis. Any oligo- or polynucleotide able to offer a C-C-C-sequence at the 3'-terminus and a second C-C-C-sequence in a defined steric position to Qbeta replicase is an efficient template. Corresponding chemical modifications convert non-template RNAs to template RNAs.


Methylation of messenger RNA of Newcastle disease virus in vitro by a virion-associated enzyme. Purified Newcastle disease virus contains an enzyme that incorporates the methyl group from S-adenosyl-L-methionine into RNA synthesized in vitro by the virion-associated RNA polymerase (RNA nucleotidyltransferase). Incorporation of radioactivity from S-adenosyl-L-[methyl-3H]methionine was totally dependent upon RNA synthesis. The methylation reaction was completely inhibited by S-adenosyl-L-homocysteine, suggesting the transfer of only the methyl group of S-adenosyl-methionine to RNA products. Velocity sedimentation and hybridization of the in vitro product RNA indicated that both [3H]methyl and [32P]GMP labels resided in single-stranded 18S RNA molecules which were virus specific. Approximately 1 to 2 methyl groups were incorporated per RNA molecule. DEAE-cellulose chromatography of product RNA after alkaline hydrolysis suggested that the 5' terminus was the site of methylation.


Protein-water interaction studied by solvent 1H, 2H, and 17O magnetic relaxation. Previous studies of the magnetic field dependence of the magnetic relaxation rate of solvent protons in protein solutions have indicated that this dependence (called relaxation dispersion) is related to the rotational Brownian motion of the solute proteins. In particular, the dispersion of the longitudinal (spin-lattice) relaxation rate 1/T1 shows a monotonic decrease with increasing field, with an inflection point corresponding to a proton Larmor frequency which is inversely proportional to the orientational relaxation time of the protein. We have now compared the relaxation dispersion of solvent 1H, 2H, and 17O In aqueous solutions of lysozyme (molecular weight 14,700) and 1H and 2H in solutions of hemocyanin (molecular weight 14,7 00) and 1H and 2H in solutions of hemocyanin (molecular weight 9 x 10(6)). The main experimental observation is that the dispersion of the relaxation rates of the three solvent nuclei in lysozyme solutions, normalized to their respective rates in pure water, is essentially the same. This is also true for 1H and 2H relaxation in hemocyanin solutions. These results confirm that entire solvent water molecules, rather than exchanging protons, are involved in the interaction. We have been unable to deduce the correct mechanism to explain the data, but we can eliminate several interaction mechanisms from consideration. For example, all observations combined cannot be explained by a simple two-site model of exchange, in which water molecules are either in sites on the protein with a relaxation rate characteristic of these sites, or else in the bulk solvent (the observed relaxation rate being the weighted average of the two). Also eliminated is the class of models in which the protein molecules induce a preferential partial alignment of neighboring solvent molecules, for example by electrostatic interaction of the electric dipole moments of the water with the electric fields produced by surface charges of the protein molecules. In addition, the idea that relaxation of solvent nuclei is due, in the main, to interactions with protein protons is precluded. Rather, it appears that the protein molecules influence the dynamics of the motion of solvent water molecules in their neighborhood in a manner that imposes on all the solvent molecules a correlation time for their orientational relaxation which equals that of the solute proteins.


Isolation of a cationic polypeptide from human serum that stimulates proliferation of 3T3 cells. A basic polypeptide that stimulates DNA synthesis and cell division in confluent populations of mouse Balb/c-3T3 cells has been isolated from whole human serum, and has been separated from the heterogenous group of molecules with insulin-like activity. This highly purified basic polypeptide has a molecular weight of 1.3 x 10(4) and an isoelectric point of 9.7. Approximately 10(7) polypeptide molecules in the growth medium allow the replication of one density-inhibited cell.


Apparent dependence of interactions between cytochrome b5 and cytochrome b5 reductase upon translational diffusion in dimyristoyl lecithin liposomes. Dimyristoyl lecithin liposomes, containing cytochrome b5 reductase (NADH:ferricytochrome b5 oxidoreductase, EC 1.6.2.2) and varying amounts of cytochrome b5, were used to measure flavoprotein catalysis alone and catalysis requiring electron transfer between the reductase and cytochrome as a function of temperature. Whereas flavoprotein catalysis showed a simple linear temperature dependence in an Arrhenius plot, the reaction involving electron transfer between the two bound enzymes showed a marked, 4-fold, change in rate at the crystalline-liquid crystalline phase transition of the hydrocarbon chains of the lecithin vesicles and a second, minor change involving the minor transition. These data represent strong evidence that protein-protein interactions in this membrane model system are dependent upon translational diffusion of nonpolar segments of the proteins in the hydrocarbon region of the phospholipid bilayer.


Chromatin architecture: investigation of a subunit of chromatin by dark field electron microscopy. Dark field scanning electron microscopy of unstained, unfixed samples of chromatin, histone-1-depleted chromatin, and nucleohistone has been used to identify an apparent subunit of chromatin, namely a disk-shaped structure we term the unit particle, which is probably about 135 A wide and 50 A thick in the hydrated state. The unit particles are found at rather uniform intervals along thin DNA-like fibers. Histone 1 depletion leads to a bimodal distribution of these spacings. Our observations suggest that the unit particle consists of a loop of nucleoprotein, perhaps around a histone core.


Hemoglobin synthesis in somatic cell hybrids: coexpression of mouse with human or chinese hamster globin genes in interspecific somatic cell hybrids of mouse erythroleukemia cells. Somatic cell hybrids were derived by fusion of mouse erythroleukemia cells with fractionated human marrow enriched in erythroblasts, or with chinese hamster fetal liver erythroid cells. Such interspecific hybrid cells, when isolated in suspension culture, had retained nearly all the mouse chromosomes and had lost most of the human or chinese hamster chromosomes. However, two such hybrids (one human, the other hamster) studied 4-6 weeks after fusion, were found to contain several non-mouse chromosomes. RNA extracted from the human marrow x erythroleukemia hybrid annealed equally to both human and mouse globin complementary DNA, indicating that coexpression of the globin genes of each species had occurred in the hybrid cells. Mouse and human mRNA were found to accumulate only after incubation of the cells in 2% dimethylsulfoxide. The chinese hamster x erythroleukemia hybrid appeared to contain a double complement of mouse chromosomes in addition to several chinese hamster chromosomes. After 7 days of incubation in 2% dimethylsulfoxide, [3H]leucine was incorporated into chinese hamster beta-globin and the mouse globin chains. Thus, globin genes from differentiated cells, when introduced into spontaneously proliferating erythroleukemia cells, may be expressed after exposure of the resulting hybrid cells to an agent capable of inducing hemoglobin synthesis in the erythroleukemia cell.


Microfibril assembly by granules of chitin synthetase. Purified preparations of chitin synthetase (EC 2.4.1.16; UDP-2-acetamido-2-deoxy-D-glucose:chitin 4-beta-acetamidodeoxyglucosyltransferase), capable of forming microfibrils in vitro, were isolated from yeast cells of Mucor rouxii. Chitin synthetase was obtained either by substrate-induced liberation of bound enzyme (54,000 x g pellet) or by isolation of unbound enzyme present in the 54,000 x g supernatant of a cell-free extract. Both preparations contained ellipsoidal granules from about 350 to 1000 A diameter. Many granules exhibited a marked depression. No typical unit membrane profiles appeared in thin sections of glutaraldehyde/OsO4-fixed samples. Upon incubation with substrate and activators, chitin microfibrils were produced. The microfibrils were often found intimately associated with granules. The most common configurations were: a microfibril with a granule at one end, or two microfibrils "arising" from the same granule. These findings lend support to the granule hypothesis for the elaboration of cell wall microfibrils by end-synthesis.


Association of high-molecular-weight proteins with microtubules and their role in microtubule assembly in vitro. High-molecular-weight components (HMW) specifically associated with microtubule protein purified from porcine brain tissue were separated from tubulin by DEAE-Sephadex ion exchange chromatography. Analysis by viscometry, sedimentation, and electron microscopy of the unfractionated microtubule protein, separated HMW and tubulin fractions, and reconstituted mixtures showed that HMW promoted formation of ring structures at 5 degrees and tubule polymerization at 37 degrees. The HMW reassociated with tubulin and was identified in thin sections as 18.9 x 5.6 nm projections attached to the microtubules with a longitudinal periodicity of 32.5 nm. These studies: (1) indicate that the HMW fraction stimulates microtubule assembly by facilitating the formation of ring structures which are apparently intermediates in polymerization, and (2) demonstrate that the HMW associates with microtubules as a structural component projecting from the surface of the microtubule wall.


Establishment of tight junctions between epithelial cells. Epithelia serve as barriers to the diffusion of solutes between body compartments, and must do so despite the frequent loss of cells. When single cells are experimentally removed from the Necturus gallbladder epithelium, contiguous cells migrate to fill the defect within 30 min. Electrophysiological measurements show that the local electrical resistance across the epithelium in the region of a wound returns to normal in the same period of time; electron microscopy demonstrates that tight junctions are formed concurrently. Physiologically functional and morphologically recognizable tight junctions can thus be established within 30 min, demonstrating a mechanism for the rapid restoration of epithelial integrity after cell loss.


Myogenesis of avian striated muscle in vitro: role of collagen in myofiber formation. The complex chemical environment required for the development of the myofiber (myotube) from embryonic avian muscle myoblasts in vitro has been simplified. Myotube formation is shown to occur in the presence of insulin, a low-molecular-weight (fusion) factor obtained from embryo extract, and a collagen substratum. In the absence of collagen, globular structures are formed which are microscopically identical to the globular syncytial structures previously described [de la Haba and Amundsen (1972) Proc. Nat. Acad. Sci. USA 69, 1131-1135]. A high-molecular-weight fraction from embryo extract will also promote myotube formation in the presence of the fusion factor. This fraction is shown to contain (a) collagen, which promotes myotube formation, and (b) an additional factor which also promotes myotube formation, and which we tentatively hypothsize to be an inducer of collagen synthesis by myogenic cells.


Biosynthesis of delta-aminolevulinic acid from the intact carbon skeleton of glutamic acid in greening barley. The customary route in animals and bacteria for delta-aminolevulinic acid biosynthesis is from glycine and succinyl CoA, catalyzed by the enzyme delta-aminolevulinic acid synthetase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37]. Attempts to demonstrate this route in plants have been unsuccessful. Evidence is given for a new enzymic route of synthesis of delta-aminolevulinic acid in plants. This route involves the incorporation of the intact five-carbon skeleton of glutamic acid into delta-aminolevulinic acid. Demonstration of the new pathway in plants has been made by feeding specifically labeled [14C]glutamic acid to etiolated barley shoots greening in the light. In the presence of levulinate, a competitive inhibitor of delta-aminolevulinic acid dehydrastase [porphobilinogen synthase; delta-aminolevulinate hydro-lyase (adding delta-aminolevulinate and cyclizing); EC 4.2.1.24], delta-aminolevulinate accumulates. The delta-aminolevulinate formed was chemically degraded by periodate to formaldehyde and succinic acid. The C5 (formaldehyde) fragment was separated, as the 5,5-dimethyl-1,3-cyclohexanedione (dimedone) derivative, from the C1-C4 (succinic acid) fragment. The C5 atom contained radioactivity predominantly derived from C1 of glutamic acid. Conversely, the labeled C3 and C4 atoms of glutamic acid were found primarily in the succinic acid (C1-C4) fragment of delta-aminolevulinate. This labeling pattern for delta-aminolevulinic acid is consistent with a biosynthetic route utilizing the intact five-carbon skeleton of alpha-ketoglutarate, glutamate, or glutamine, and is inconsistent with the delta-aminolevulinic acid synthetase pathway utilizing glycine and succinyl CoA as precursors.


Feedback dynamics analysis of secondary successional transients in ecosystems. A theoretical dynamic model of the mutual causalities that generate secondary successional behavior in ecological systems is developed using zero- and first-order nonlinear difference equations. The model is based on Odum's tabular model of ecological succession, and has been simulation-tested for the case of secondary succession in a grassland ecosystem. It shows how energy, abiotic and biotic matter, and community (species) diversity interact in time and space to produce autogenic succession, that is, developmental changes generated by biotic components within the system as distinguished from allogenic forcing functions from without the system. The simulations demonstrate that successional transients can arise from the endogenous feedback structure of the ecosystem and provide strong evidence for the validity of the model.


Interlocus variation of genetic distance and the neutral mutation theory. Theoretical distributions of genetic distance between reproductively isolated taxa are derived by means of computer simulation, taking into account mutation and random genetic drift. The distributions obtained are in good agreement with the observed distributions of interracial and interspecific genetic distances for enzymes loci in Drosophila. This indicates that the gene substitution at enzyme loci can be explained by the neutral mutation theory.


Distribution of allelic frequencies in a finite population under stepwise production of neutral alleles. A formula for the distribution of allelic frequencies in a finite population is derived assuming stepwise production of multiple alleles. Monte Carlo experiments were performed to check the validity of the formula, and excellent agreement was obtained between theoretical distribution and experimental results. The formula should be useful for analyzing genetic variability in natural populations that can be detected by electrophoretic methods.


Interaction of lymphocytes with lipid bilayer membranes: a model for lymphocyte-mediated lysis of target cells. Horizontal lipid bilayer membranes were used as a model system to study lymphocyte-mediated killing of target cells. Dinitrophenylated lipid bilayers can physically support dozens of lymphocytes for periods of over one hour without breakage or increasing the electrical conductance of the membrane. However, in the presence of antibody against Dnp, human lymphocytes rapidly induced increases in membrane conductance of several orders of magnitude without membrane breakage. Such ionic permeability increases occurred only when the membrane voluage was positive on the lymphocyte side, as would be the case with a target cell membrane. The lymphocyte and antibody dependence of this conductance increase parallels that observed for lymphocyte killing of antibody-coated target cells. The results are interpreted as evidence that the primary event in lymphocyte killing of antibody-coated target cells is the creation of ion-conducting channels in the target membrane.


Antigen-induced conformational changes in antibodies and their Fab fragments studied by circular polarization of fluorescence. Conformational changes induced in antibody molecules and in their Fab fragments by binding of antigen were investigated by the circular polarization of the fluorescence emitted by the tryptophan residues. This property of the fluorescence is related to the asymmetry, and thus to the conformation and environment, of the emitting chromophore. Changes in the circular polarization of the fluorescence of the antibody were observed upon binding of RNase to anti-RNase, of poly(DL-alanyl)-poly(L-lysine) to antipoly(D-alanine), and of the "loop" of lysozyme, a monovalent antigenic determinant, to anti"loop." The spectral changes were observed at different antigen-antibody ratios, including high antigen excess, indicating that they are due to antigen binding and not to aggregation. The circular polarization of fluorescence also detects changes in conformation of the different Fab fragments upon binding of the corresponding antigens. These changes in conformation were, however, markedly different from those observed for the whole antibody molecules, and indicated an interaction between the Fc and Fab fragments in the antibody molecule, and probably a change in the conformation of Fc upon binding of antigen to the antibody. In contrast, the small hapten, phosphorylcholine, did not induce a change in the circular polarization of the fluorescence of its antibody or corresponding Fab fragments. Reduction of the interchain disulfide bonds of the antibodies abolished the antigen-induced spectral changes due to the presence of the Fc portion in the molecule, but not the changes observed in Fab, suggesting that the disulfide bonds at the hinge region of the antibody are required for the transmission of the conformational change from the Fab to the Fc.


Lysis of leukemia cells by spleen cells of normal mice. Spleen cells from 2- to 3-month-old normal mice of some strains having a low incidence of spontaneous leukemia were found to lyse cells of the spontaneous AKR leukemia K36 in the 51Cr release assay. Incubation of 51Cr-labeled ADR K36 cells with spleen cells from normal C57BL/6, C57L, C57BL/10, and RF mice resulted in the release of significantly more 51Cr than that released in the presence of medium alone. In contrast, 51Cr released from AKR K36 cells after incubation with spleen cells from mice of the high leukemic strains AKR and C58 was less than that released spontaneously. The results of competitive inhibition tests when C57BL/6 spleen cells were incubated simultaneously with 51Cr-labeled AKR K36 target cells and varying numbers of nonlabeled cells demonstrated that the cytotoxic activity of normal C57BL/6 spleen cells was directed against an antigen(s) associated with several leukemias, but that was undetectable on normal thymocytes. Pretreatment of C57BL/6 spleen cells with carbonyl iron and a magnet, which removed phagocytic macrophages, did not decrease the cytotoxic acitivity for AKR K36 cells.


Methylmalonicacidemia: biochemical heterogeneity in defects of 5'-deoxyadenosylcobalamin synthesis. We measured the synthesis of 5'-deoxyadenosylcobalamin (AdoCbl) in fibroblast extracts from patients with inherited methylmalonicacidemia due to deficient activity of the cobalamin-dependent holoenzyme, methylmalonyl-CoA mutase (EC 5.4.99.2). Previous studies with intact fibroblasts from patients whose holoenzyme deficiency was secondary to abnormal cobalamin metabolism had defined two phenotypes, one in which whole cells failed to accumulate AdoCbl and a second in which they failed to accumulate both AdoCbl and the second cobalamin coenzyme, methylcobalamin. With a broken cell assay of AdoCbl synthesis in cell extracts and the cell lines are named cbl A mutants; the other class shows severe deficiency of AdoCbl synthesis and the cell lines are named cbl B mutants. We define cbl C mutants as those in which both AdoCbl and methylcobalamin fail to accumulate in intact cells. The assay for AdoCbl synthesis is thought to measure two enzymatic activities, cob(II)alamin reductase (EC 1.6.99.9) and cob(I)alamin adenosyltransferase (EC 2.5.1.17). Subcellular fractionation studies place this combined activity in mitochondria.


Fetal mouse hearts: a model for studying ischemia. A new experimental model for the study of two important aspects of ischemia, namely, oxygen and substrate deprivation, is proposed: the intact, beating fetal mouse heart in organ culture. This model offers long-term stability, ease and reproducibility of preparation, and the ability to manipulate experimental conditions. Hearts deprived of oxygen and glucose ceased beating immediately. After 3-4 hr of deprivation, biochemical and ultrastructural changes consistent with ischemic injury were evident. These include depletion of ATP and glycogen levels, loss of cytoplasmic enzymes, and extensive swelling and disruption of mitochondrial structure. Glucose and insulin partially protected against ATP depletion. Upon resupply of oxygen and glucose , beating resumed immediately, ATP levels rapidly increased to control levels and, consistent with this, mitochondrial structure returned toward normal. During the recovery phase autophagic vacuoles containing damaged mitochondria and myofibrils were seen, indicating that repair mechanisms were activated. Consistent with this, the proportion of lysosomal enzymes that were present in the nonsedimentable fraction of the tissue homogenate increased. We conclude that the cultured fetal mouse heart is a model useful for studying myocardial responses to anoxia and/or substrate deprivation and for assessing interventions designed to limit damage or to stimulate repair after ischemic injury.


Individual odor differences and their social functions in insects. The evolution of individual or subgroup differences in odors of halictine bees is suggested from possible widespread intraspecific variation in pheromones. An important result of such variation may be maintenance of genetic polymorphisms; in nesting Hymenoptera odor differences may also facilitate individual nest recognition. In Lasioglosum zephyrum males habituate to odors of different females and perhaps thus save time by not trying to copulate with nonreceptive individuals. Guards (females) at nest entrances distinguish their few nestmates (other females) from other conspecific individuals by odors, seemingly pheromones. Duration of the habituation in L. zephyrum is at least an hour (perhaps much more) for males in relation to females and 6 or 7 days for guards in relation to nestmates. Studies of pheromones should take into consideration the possibility of pheromonal polymorphism in any species and the likelihood that it may be significant from biological and practical viewpoints.


Slow growth rate of a deep-sea clam determined by 228Ra chronology. The age of a deep-sea clam, Tindaria callistiformis, from 3803 m depth has been determined by 228Ra (6.7 year half-life) chronology of separated size fractions of a captured population. A length of 8.4 mm is attained in about 100 years. Shells of this size fraction show about 100 regularly spaced bands, indicating that the growth feature may be an annual one.


Ontogenesis of a biological clock for serotonin:acetyl coenzyme A N-acetyltransferase in pineal gland of rat. Serotonin:acetyl coenzyme A N-acetyltransferase (EC 2.3.1.5) Activity in pineal gland was assayed in rats which were born and raised under diurnal lighting conditions, in continuous darkness, or in constant light. N-Acetyltransferase activity in the pups raised under diurnal lighting showed a rhythmic pattern, with high enzyme activity during dark period. The pups raised in continuous darkness also showed a rhythmic pattern, the phase of which was delayed by 8 hr in 7-week-old pups; the rhythmic phase of N-acetyltransferase began in the evening in 12-day-old pups and was regularly delayed by 1 hr every week. The pups raised in constant illumination also showed a rhythmic pattern; the rhythmic phase was delayed by 3 hr every week. When the mother rats were coupled in darkness and maintained in darkness during pregnancy and after the pups were born, their pups again showed a rhythmic pattern. These observations indicate that the biological clock for N-acetyltransferase is generated independently of environmental lighting. When mothers were coupled under reversed lighting conditions and transferred into darkness or light, the rhythmic pattern in their pups was inverted 180 degrees from that of pups born of diurnal mothers. When the pups were raised in darkness, the rhythmic phase of N-acetyltransferase in the pups was similar to that of their mothers. It is suggested that in the absence of light-darkness cycle, the mother rat sets the rhythm of the pups to synchronize with her own rhythm. When pups were reared by a foster mother with a different rhythmic pattern from that of their original mother, the rhythmic phase in the pups was closer to that of the original mother, suggesting that the original mother plays the predominant role setting the rhythm of the pups.


Glycogen metabolism in human skin fibroblasts. Influence of maltose on the activity of acid alpha-1, 4-glucosidase. Maltose added to medium in a concentration of 100 mg/100 ml enhances the hydrolytic activity of acid alpha-1, 4-glucosidase in skin fibroblasts in culture derived from normal human subjects, but under the same conditions maltose has no demostrable effect on the enzyme in fibroblasts derived from skin of patients with Cori Type II glycogenosis. Upon addition of maltose to Cori Type II fibroblasts there is a marked decrease of glucose in medium overlying the cells with a concomitant marked increase in glycogen content of the same cells. Glycogen decreases in a similar manner in both normal and mutant cell types after 16 days in culture. This apparent utilization or degradation of glycogen in Cori Type II fibroblasts in culture is difficult to explain unless only a proportion of the polysaccharide accumulates within lysosomes. We propose, therefore, that extra-lysosomal glycogen which accumulates in fibroblasts from Cori Type II glycogenosis may be more easily degraded by glycogenolytic cytoplasmic enzymes, particularly in cells grown for as long as 2 wk in glucose-starved media.


An effect of chlorhexidine and two related drugs on glycosaminoglycans in rat skin. The aim of the present investigation was to estimate the local effect of three plaque-inhibiting drugs on some glycosaminoglycans in rat skin. The drugs comprised chlorhexidine, dichlorhexidine, and trichlorhexidine; and the glycosaminoglycans examined were hyaluronic acid, chondroitin sulfate, and heparin. Glycosaminoglycans were measured by the carbazole method. Upon subcutaneous injections in rats, chlorhexidine, dichlorhexidine, and trichlorhexidine caused marked reductions in the surrounding skin's content of total hexosamine as well as of the three types of glycosaminoglycans. No significant difference could be demonstrated between the different types of glycosaminoglycans in this respect.


The effectiveness of a synthetic vasopressin analogue as a vasoconstrictor. The effectiveness of a synthetis vassopressin analogue, ornithine-8-vasopressin (POR-8), as a vasocontrictor was tested in the superficial vessels of the rabbit ear. When compared to a control of normal saline and a standard of a dilute solution of epinephrine in lidocaine, POR-8 in saline is more effective than POR-8 in lidocaine, and is comparable in its effectiveness to the epinephrine solution.


Chromosome constitution of cells from human gingiva. This is a study of cells and chromosomes during serial transfer of tissue cultures, starting from the first mitosis occurring before explantation of normal gingival tissues and continuing until a genotypic variation was attained after explantation. From 16 specimens, 9 could be maintained in vitro for varying lengths of time, 7 for more than 50 weeks. In all cases, at 2 months in cultures and afterward, cells were found to be fibroblast-like cells with heteroploid chromosomal complement. The heteroploidy of the cells was due to extrasomy of chromosomes from all groups. However, chromosomes of the  me cells before culturing showed the normal diploid number of 46 chromosomes.


Pharmacological aspects of the N2O-O2 experience. Part 1. Conceptual framework.


The parakeratin layer of zinc-deficient rat buccal epithelial. Weanling rats were fed a zinc-deificient diet, 1.3 ppm zinc, for four weeks. Parakeratotic changes of the buccal epithelium were studied by electron microscopy. The incomplete disintegration of the nucleus and cytoplasmic organelles in the horny layer is deemed to be due to insufficient function of zinc-related lytic enzymes.


Acute promyelocytic leukemia.

Acute promyelocytic leukemia.


Mandibular anterior crowding in relation to tooth size and craniofacial morphology. In the present study the problem of mandibular anterior crowding was investigated by comparing a group of adults having approximately ideal occlusion (n = 27) with a group with  corresponding occlusion except for a slight crowding in the mandibular anterior segment (n = 39). Both sexes were represented. A statistical evaluation revealed that in the latter group the mesiodistal diameter of the four mandibular incisor teeth was significantly greater, whereas the intercanine width and the frequency of third molars were the same in both groups. A comparison of the craniofacial morphology of the two groups displayed limited differences, and only the basal sagittal jaw relationship and the mandibular inclination differed significantly. No significant correlations were observed between the space conditions and any of the variables studied.


A morphologic description of a dry skull with mandibulofacial dysostosis. The morphology of an East Indian, dry skull exhibiting the characteristics of mandibulofacial dysostosis (MFD) is described. The skull was small, but the shape of the calvarium was essentially normal. Extensive anomalies were registered in the sphenoid bone, the temporal bone, the zygomatic bone, the maxilla, and the mandible. A lateral cephalometric radiograph of the skull was compared with a mean value diagram of adult Danish males in order to illustrate the morphologic aberrations of the MFD skull. The etiology and pathogenesis of the syndrome are disucssed.


Application of chlorhexidine by oral irrigation systems. Low concentrations of chlorhexidine (0.006%) were found to inhibit plaque formation when 750 ml was applied twice daily by oral irrigation systems. The procedure took 1-2 min and may be a convenient method of maintaining oral hygiene in patients in whom normal mechanical cleansing is difficult.


Sealing properties of intermediary bases and effect on rat molar pulp. Five "cream-like" intermediary bases (Hypocal¿, Dycal¿, Reocap¿, Cavitec¿ and Dropsin¿) were studied using ZnO-eugenol (ZOE) and phosphate cement for comparison. The in vitro experiments, which were designed to reveal the penetration of a dye and an etching liquid, showed that Dropsin and Hyypocal were permeable to dye and that Dropsin was permeable to acid as well. The in vivo experiments revealed no definite differences between the different cream-like base materials, nor were there differences between those and the conventional cements. The overall mildness of the dentin-pulp reactions and the suitability of the rat molar for this kind of research are discussed.


Emotional factors in juvenile diabetes mellitus: a study of the early life experiences of eight diabetic children. The developmental history of eight diabetic children was compared with that of their nondiabetic siblings. On the basis of data obtained through interviews with the children and their families, as well as a chart review, we advance the hypothesis that an as yet unspecified metabolic "pre-diabetic" pathophysiological condition may be reflected in disturbances of appetite, satiation and weight regulation appearing early in life in those children who may later develop clinical diabetes mellitus. We further hypothesize that these dysfunctions are accompanied by a disturbance in important psychological developmental processes, compounding the liability a physiologically susceptible individual suffers. The results are discussed in terms of previous psychosomatic research.


Does a drug-induced stimulation of diazepam metabolism exist? (A preliminary report).


Ultrastructural study of erythrophagocytosis in the rat bone marrow. I. Red cell engulfment by reticulum cells. Previous light microscopic studies have revealed the erythroclastic potential of the rat bone marrow reticulum cells, and call for ultrastructural study of the finer details of this process. Electron microscopy of rat bone marrow which had been stimulated to increase its erythrophagic activity, either by splenectomy or by transfusion of heat denatured erythrocytes, confirmed the central reticulum cell of erythroblastic islands as the main phagocytic cell in bone marrow erythroclasia. The early digestive vacuoles, which are formed by the fusion of erythrophagic vacuoles with lysosomes, correspond to the acidophilic, globular structures which characterize erythrophagocytosis as observed by light microscopy. By forming intrasinusoidal protrusions, the bone marrow reticulum cells engulf circulating effete red cells. The engulfed red cells are then transported intracellularly across the sinusoidal wall for final disintegration in the intraparenchymal part of the reticulum cell. This transmural mode of erythrophagocytosis by reticulum cells most probably demonstrates the fundamental phagocytic mechanism of the bone marrow part of the reticulo-endothelial system. Transmural transport of reticulocytes adherent to reticulum cells during the formation of protrusions illustrates a possible mechanism for liberation of red cells from the bone marrow.


Ultrastructural study of erythrophagocytosis in the rat bone marrow II. Iron metabolism in reticulum cells following red cell digestion. Intracellular transport and storage of iron in bone marrow reticulum cells can be studied in the electron microscope by the recognition of iron macromolecules. Following artificially increased bone marrow erythrophagocytosis ferritin molecules accumulate both in the cell sap and in the lysosomes of erythroclastic reticulum cells. Persistent iron loading transforms lysossomes into siderosomes, after which haemosiderin may be formed by grandual transformation of ferritin. The bone marrow reticulum cell shows evidence suggestive of autophagy, a process which may allow for the transfer of cell sap ferritin into lysosomes, as documented for other types of iron storing cells.


Erythrocyte pyruvate kinase activity in patients with haematological malignancies. Erythrocyte pyruvate kinase (PK) activity was decreased with acute myelomonoblastic leukaemia (AML) and lymphosarcoma cell leukaemia (LSAL) but increased in patients with chronic myelocytic leukaemia (CML). There was no difference in the enzyme activity between controls and relatives of patients with AML. PK activity in patients with ALL during complete remission was higher than during untreated and relapsed stages. These data provided evidence that the altered enzyme activity is acquired rather than genetic. There was a positive correlation between PK activity and red cell creatine levels. The red cell creatine was low in patients with AML but high in patients with CML. This suggests that the altered enzyme activity in these patients is at least part due to red cell age.


The ultrastructure of spontaneous radial segmentation of the nuclei in bone marrow cells from 3 patients with acute myeloid leukaemia. Bone marrow cells with spontaneous radial segmentation of the nuclei from three patients with acute myeloid leukaemia were analysed by means of electron microscopy. The centriole was found in the centre of the cluster of nuclear segments. Cytoplasmic microtubules were found in the intersegmental clefts and in the pericentriolar area. The present observations support the hypothesis that spontaneous radial segmentation of the nuclei in tumour cells is due to a microtubule-associated contractile process, by which the nucleus is folded into segments.


A study of the food consumption by the duplicate portion technique in a sample of the Dalby population, Sweden.


L-asparaginase and prednisolone pretreatment followed by rubidomycin and cytosine arabinoside for induction of remission in adult patients with acute myeloblastic leukaemia. 77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with 1-asparaginase and prednisolone followed by  a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without 1-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with 1-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with 1-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.


Postural position of the manible with special reference to instruction, head fixation and relaxation. I. Significance of instruction.


Loa loa infection without microfilaraemia.


Chronic myeloid leukaemia in Zambians.

Chronic myeloid leukaemia in Zambians. Sixteen Zambian Africans with chronic myeloid leukaemia are described. Clinical and haematological features were unremarkable except for the relative extreme youth of three patients (aged 18 years or less) and one patient with the aleukaemic form in whom the diagnosis was proved by marrow examination. Thirteen patients were treated with busulphan (Myleran), of whom 12 showed varying degrees of responsiveness, and one was completely resistant both to busulphan and cyclophosphamide. One patient became pregnant while receiving busulphan and another showed depression of spermatogenesis when investigated four years after start of treatment. The poor responsiveness of some Africans to busulphan is briefly speculated upon.


Synergism between metichlorpindol and methylbenzoquate against E. acervulina.


Splanchnic oxygen uptake in relation to systemic oxygen uptake during postoperative splanchnic blockade and postoperative fentanyl analgesia. In 34 patients with gallbladder disease, but otherwise healthy, the systemic and splanchnic oxygen uptake were studied in connection with cholecystectomy. Postoperatively, 22 patients were given a posterior splanchnic blockade with 0.5% plain lidocaine, and 12 were given fentanyl intramuscularly in a dose of 3.5 mug/kg b.w. Postoperatively, before the analgesic agent was administered, both the systemic and splanchnic oxygen uptake were increased by 40--50%, the splanchnic fraction of the systemic oxygen uptake being the same as preoperatively. Following administration of fentanyl, as well as after splanchnic blockade, the systemic oxygen uptake decreased almost to the preoperative level. The splanchnic oxygen uptake, however, did not change after fentanyl administration but increased further significantly following splanchnic blockade. The splanchnic fraction of the systemic oxygen uptake increased rapidly after the blockade, while it increased slowly after fentanyl administration.


Effects of abdominal surgery under general anaesthesia and of postoperative analgesic therapy on splanchnic exchange of some blood borne energy metabolites. Sixteen patients with gallbladder disease, but otherwise healthy, were studied in connection with cholecystectomy. For postoperative analgesia, seven patients were given a posterior splanchnic blockade, 30 ml of 0.5% plain lidocaine, and nine patients were given fentanyl intramuscularly in a dose of 3.5 mug/kg b.w. Immediately after the operation and before analgesia, the arterial blood concentrations of glucose, lactate, glycerol, 3-hydroxybutyrate, and free fatty acids increased significantly. The splanchnic exchange of these metabolites was also significantly increased, except for glucose, the splanchnic release of which was significantly reduced. Induction of analgesia, both methods, was followed by a rapid significant decrease of the arterial blood concentration of glycerol, which tended to rise later when the analgesia disappeared. The arterial blood concentration of glucose and lactate showed a tendency to decrease slowly following both kinds of analgesia, while the arterial blood concentration of 3-hydroxybutyrate remained stable. The splanchnic release of glucose was significantly reduced after administration of fentanyl, while it increased significantly following splanchnic blockade, the splanchnic glucose release being correlated to arterial blood pH. The splanchnic release of 3-hydroxybutyrate was significantly reduced during maximal analgesia in both groups. The splanchnic uptakes of glycerol and free fatty acids were correlated to their splanchnic inflows.


Hormonal patterns in vaginal smears from puerperal women. Maturation indices were determined for 1,000 vaginal smears from women three weeks to nine months postpartum. Atrophic smears predominated three to six weeks after delivery in women who were lactating, but only one-third of the non-lactators had an atrophic pattern during those weeks. There was a progressive increase in the incidence of estrogenic patterns observed beyond the sixth postpartum week, irrespective of the persistence of lactation. The incidence of mixed patterns (equal numbers of parabasal, intermediate and superficial cells) was remarkedly constant (about 5 per cent) regardless of lactation or time beyond delivery. This study confirms the traditional view of hormonally related puerperal vaginal cytologic patterns, and is at variance with recent claims that vaginal atrophy is unusual in the puerperium.


I. Validity of dichnomatic earpiece densitometry for quantitative studies in children with shunt-free cardiovascular malformations. Cardiac output was assessed in 16 children without evidence of cardiovascular shunts from simultaneously recorded earpiece and cuvette densitometric tracings. The earpiece set-up was calibrated by the end-tail method. Both instruments gave linear response to dye concentrations used. There was a close correlation between cardiac output figures recorded by the two methods (r equal to 0.95) and no systematic difference occurred. It is concluded that in infants and children earpiece densitometry constitutes a rapid and accurate method for quantitative circulatory studies.


V. Exercise studies in children with congenital heart disease. An earpiece densitometric investigation. Twenty-three patients have been studied by exercise testing during right heart catheterization. Cardiac output was measured by the earpiece densitometric technique before, during and after the exercise period. It is concluded that the earpiece densitometric technique in conjunction with exercise testing offers an attractive alternative for the study of pressure and flow characteristics in children with congenital heart disease.


Postoperative hepatic blood flow and its relation to systemic circulation and blood gases during splanchnic blockade and fentanyl analgesia. Thirty-four patients with gallbladder disease, but otherwise healthy, were studied in connection with cholecystectomy. For postoperative analgesia, 22 patients were given a posterior splanchnic blockade with 0.5% plain lidocaine, and 12 were injected intramuscularly with fentanyl in a dose of 3.5 mug/kg b.w. Postoperatively, before administration of the analgesic agent, the cardiac output, mean arterial blood pressure, heart work and estimated hepatic blood flow were increased and the total peripheral resistance, splanchnic vascular resistance, arterial oxygen tension and base excess values were decreased. Fentanyl, in addition to its analgesic effect, also decreased the arterial oxygen tension and pH and increased the arterial carbon dioxide tension. There was little change in cardiac output, mean arterial blood pressure and estimated hepatic blood flow. Following splanchnic blockade, on the other hand, pain relief was accompanied by a decrease in cardiac output, mean arterial blood pressure and heart work to about the preoperative level, while the estimated hepatic blood flow remained unchanged and the splanchnic vascular resistance decreased rapidly. Neither total peripheral resistance nor blood gases altered as a result of splanchnic blockade.


Mixed-image planimetry. Assessment of a new method for stereometric analysis in microscopy. A new method for stereometric measurement of surface area in microscopy is described, based on the mixed-image principle. The measurement was accomplished by observing the area on which was superimposed the image of a miniature electric lamp attached to an ordinary planimeter. Mixed-image planimetric measurements were more easily made and required much less time than area calculation by an integrating eyepiece, by weight or by ordinary planimetric measurements of photomicrographs or tracings of the area. Mixed-image planimetric measurements of a finite area varied less than 1 per cent. Such precision was not obtained with the other methods. The new method was devised in vivo stereometric measurements of bone tissue remodelling in rabbit ear chambers, but should find a much wider application in quantitative microscopy of both finite and extensive objects.


II. Cardiac output studies in infants and children undergoing right heart catheterization. Cardiac output figures from 97 patients were computed by earpiece densitometry and correlated to various dimensional parameters. Stroke volume was better correlated to body dimensions than cardiac output indicating that patients undergoing right heart catheterization were not in basal state.


Pectus excavatum; a clinical study with long term postoperavtive follow-up. There are divergent views about the harm that pectus excavatum and related chest deformities does to the respiratory and heart function. The indications for surgery and the optimal age for surgical intervention are debatable. In this study 37 operated and 38 nonoperated cases of about the same severity have been followed for more than ten years and examined after the age of 18 years. The examination included socio-economic, cosmetic and cardio-pulmonary function aspects. It could be shown that from the psychological aspect there were no significant differences between the operated and the non-operated cases. The tendency to contract bronchopneumonia is not influenced by operation. The physical working capacity was the same in the two groups. The operated cases have slightly lower pulmonary function values that the non-operated in spite of the fact that the non-operated group at the time of follow-up included the more seveee cases. Age at operation did not seem to be of any importance for the long-term results. The lower pulmonary function capacity in the operated cases is thought to be attributed to a restriction secondary to the operation. There are also indications that pectus excavatum tends to become less pronounced with increasing age. The study supports a restrictive attitude towards surgery.


Ciliated bodies in gynecologic cytopathology: parasite or cellular debris? Ciliated bodies, similar to the ones described originally by Gaudefroy and Coliche, were discovered in fluid from an ovarian cyst and fluid in the Douglas pouch. These were reproduced experimentally by mucosal scraping of Fallopian tubes. In fact, they were of cellular origin from desquamation of the ciliated apical portion of columnar cells.


Myeloproliferative disorders with selective differentiation toward megakaryocytic cells. A clinicopathological study of three autopsy cases. Three autopsy cases of myeloproliferative disorders with selective differentiation toward megakaryocytic cells were reported with a clinicopathological analysis. All of these cases had some common distinctive features; (1) patients, adult of more than 40 years of age, (2) relatively acute fatal course (about 20 to 100 days), (3) continued pancytopenia in the peripheral blood, (4) so-called blast cells, occasionally showing accumulation, according to the length of total duration, in addition to overwhelming predominance of atypical megakaryocytic cells in the bone marrow, and (5) an increased tendency of fibrillosis in the interstitium of the bone marrow corresponding to the more or less prolonged duration of the course. From these facts, they should be compatible with so-called megakaryocytic myelosis. Some relationship between this disorder and myelogenous leukemia, and infiltrative tendency of megakaryocytic cells in the extramedullary organs had also been discussed shortly.


Non-visual prescreening of cervical smears with a flow-through cytophotometer. An experiment was carried out with the fluorescence impulse cytophotometer I.C.P. 11 (Phywe, Göttingen, Germany) in a routine cytology laboratory. A total of 600 cervical smears were examined with 15 test samples of body fluids and tissue cultures. The results were compared with those obtained by classical Papanicolaou cytology and clinical "follow-up". The main purpose was to find criteria for malignancy to be used as parameters in automated non-visual cytology. The main problems in the technique of preparing and measuring specimens have been discussed. Preparation of cell suspensions was time consuming; moreover, techniques were not completely controllable. A method for judging histograms was discussed. It appears that unless a better method is found for preparing suspensions of single, naked and undamaged nuclei, free from leukocytes, impulse cytophotometric measurement of DNA will remain an unreliable method for prescreening of cervical smears.


Cerebellar influences on autonomic mechanisms. An experimental study in the cat with special reference to the fastigial nucleus.


Breast and vaginal hormonal cytology in patients with breast secretions.


The cytology of transitional cell carcinoma of the urinary bladder. Urine specimens from 77 patients with transitional cell tumors of the urinary bladder, 15 patients with inflammatory lesions and five normal individuals were analyzed. The two nuclepore slides of all patients with neoplastic disease contained over 100 neoplastic cells and in one-half of the cases over 1,000 tumor cells were present. The percentage of neoplastic cells to atypical and normal cells ranged from 25 per cent for papillary carcinomas, Grade I, to 36 per cent for poorly differenciated carcinomas. There were no significant differences of the cytoplasmic features but the nuclei of malignant cells were slightly more hyperchromatic, contained significantly more nuclei and were characterized by a coarsely rather than finely granular nucleoplasm. The cell size of 5,970 cells and the nuclear size of 8,455 cells was determined by planimetry. Normal transitional cells averaged 341 square microns and were larger than those exfoliated from tumors. The mean nuclear area was 36 square microns for normal cells, 52 square microns for benign atypical cells, 54 square microns for cells from papillary carcinoma, Grade I, 78 square microns for papillary carcinomas, Grade II, and 90 square microns for transitional cell carcinoma, Grades III and IV. The study indicated that significant quantitative differences exist between normal transitional cells and those exfoliated from moderately and poorly differentiated transitional cell carcinomas. The cells exfoliated from papillomas or papillary transitional cell carcinomas, Grade I, closely resemble hyperplastic or atypical transitional cells which in turn can be differentiated from normal urothelial cells.


Anitschkow nuclear changes observed in oral smears. Squamous epithelial cells with nuclear characteristics similar to those of the "Anitschkow myocyte" have been found in smears from the oral cavity. The cells are found in scrapings from the area around the labial fold of the lower lip and are most commonly found in abundance in people with active aphthous ulcers. Electron microscopic study of material from the oral cavity is being undertaken by the ultrastructural section of our department.


The Di Guglielmo syndrome: a study of 17 cases. I. Clinical and haematological manifestations. Based on a series of 17 patients with Di Guglielmo's syndrome, i.e., erythraemic myelosis and erythroleukaemia, a description is given of the clinical and haematological manifestations of this disease. Three cases were anerythraemic, i.e. no erythroblasts were seen in the blood smears, and three were aleukaemic, i.e. no myeloblasts and/or promyelocytes were found in the blood. The percentage of erythroblasts in the bone marrow smears varied from 34 to 96. In all cases, abnormalities (often megaloblastoid changes) of varying severity were observed in the erythroblasts. Proerythroblasts showing erythrophagocytosis, multinuclearity and vacuolation of the cytoplasm are features of great diagnostic importance. Five patients had myeloblasts or promyelocytes containing Auer rods, six had neutrophilic granulocytes showing pseudo-Pelger-Hüet anomaly, and in most cases agranular polymorphonuclears were present. Brief comments are given on the PAS, nuclear arylsulphatase and naphtol-AS-D-chloroacetate-esterase staining methods. Four of five patients studied cytogenetically revealed abnormal stem lines. The survival times after the onset of the disease ranged from 17 days to 20 months. The disease is closely related to myeloblastic leukaemia. In the course of Di Guglielmo's syndrome, the leukaemic component often becomes more conspicuous, so that, in the terminal phase, the disease cannot be distinguished from typical myeloblastic leukaemia. As, in Di Guglielmo's "leukaemia", the diagnostic problems are greater than and different from those in typical myeloblastic leukaemia, it is still reasonable to place this disease in a separate group under acute granulocytic leukaemia.


Slit-scan cytofluorometry: data base for automated cytopathology.


The clinical significance of serum alkaline phosphatase isoenzymes in locomotor diseases. AP isoenzymes were estimated in 292 patients with locomotor diseases and in 124 healthy controls. The diagnostic usefulness of AP determination is increased by estimation of isoenzymes. Investigations were made to study the biological profile of organ specific AP activities: 1. Rheumatoid arthritis and Reiter's syndrome - the total AP and L-AP activities were increased. 2. Ankylosing spondylitis treated by physiotherapy - the total AP, B-AP and I-AP activities were increased. After drug therapy an increase occurred also in L-AP activity while I-AP activity showed no significant change. 3. Progressive OA of hip and knee showed increased levels of total AP and B-AP activities. 4. Degenerative diseases of the spine, chiefly cases of discopathy, showed significantly reduced levels of AP and B-AP activities. 5. In osteoporosis there was an increase in total AP, L-AP, B-AP and I-AP activities. 6. In the active generalised form of Paget's disease, increased levels were found of total AP, B-AP, I-AP and L-AP activities. 7. In neoplastic diseases the isoenzymes can help to reveal metastatic dissemination and thus aid preoperative evaluation. 8. In gout and hyperuricemic syndromes there was a relative increase of B-AP activity and non-significant fall of L-AP activity. Increased levels of L-AP occured in patients with gallbladder disease, after immunosuppressive therapy or after infectious hepatitis. A fall of L-AP levels was found after Corticotrophin and after intraarticular administration of Kenalog. Increased B-AP activities occurred after total hip replacement, in acute or chronic pyelonephritis and in active osteonecrosis and osteoporosis. Anabolic therapy caused a significant fale of B-AP activity to fall significantly. Reduced B-AP levels were also found after antibiotic therapy. Increased I-AP activity was found in cases of osteoporosis, and in secondary amyloidosis; reduced I-AP activity was seen in mucous colitis. The activity of I-AP is assumed to increase as a result of the changed intestinal calcium and phosphorus regulation occurring in association with the enhanced bone tissue metabolism. From this point of view an order of significance is given for the activity of bone pathology in the separate diagnostic groups of locomotor diseases.


Unsaturated dietary fat and lipoperoxides as etiological factors in vitamin E deficiency in mink. The prophylactic effect of vitamin E and iron compounds.


On the persistence of bacteria in manure. A field and experimental study with special reference to Salmonella in liquid manure.


Attempted orthodontic movement in the presence of suspected ankylosis. A 37-year-old man with suspected ankylosis ("submerged" teeth, radiographically obliterated periodontal membranes, and sharp or ringing percussion tests) was subjected to attempted orthodontic movement. The maxillary canine and posterior segments were chosen as treatment areas. While the terms "light" and "heavy" are relative, forces ranging from 6 to 24 ounces were variants great enough in the areas treated to have elicited movement if movement were possible. After continuous forces had been applied for 110 days, measurements showed no movement in either maxillary quadrant.


Muscles of mastication in small children: an electromyographic analysis. The temporalis, masseter, and depressor muscles of fifteen normal children were studied electromyographically to determine their activities during the position of resting tonus, during various movements of the mandible, and during the act of swallowing. Analysis of our results led to the following conclusions: 1. Resting tonus of the mandible does not depend on neuromuscular activity in the three portions of the temporalis, masseter, and depressor muscle group; they were inactive bilaterally. 2. Opening of the jaw either slowly or maximally, and against resistance, is brought about by the contraction of the depressor muscle group. 3. Closing of the jaw quickly is brought about mainly by greater contraction of the masseter muscle, and slightly by contraction of the temporalis. 4. Closing the jaw quickly with occlusal contact of the teeth is effected by the temporalis and masseter muscles. 5. Protraction of the jaw is performed by contraction of the masseter muscles. The depressor muscle group contracts to maintain the slight depression followed by the protraction. 6. Swallowing saliva and water is accompanied by contractions of the depressor muscle group. 7. Incisor chewing of gum and peanuts mainly recruits marked contraction of the masseter muscle. Some slight-to-moderate activity is achieved by the temporalis. The depressor muscle group acts in antagonism with the elevator muscles. 8. Chewing gum on the right and left molar sides and normal mastication are effected by the contraction of the temporal and masseter muscles. The suprahyoid muscle group acts in antagonism with the elevator muscles. 9. Normal children with deciduous teeth have patterns that are similar to those of normal adults.


Begg light-wire treatment of a severe class II cross-bite malocclusion.


Editorial: A new baby boom? could be!

Editorial: A new baby boom? could be!


Editorial: AAO issues special bulletin on extraoral appliance care.


A test of the transmethylation hypothesis in acute schizophrenic patients. Keeping biochemical determinations and clinical judgements independent, the authors investigated three aspects of the transmethylation hypothesis. They found that 26 acutely schizophrenic patients were no more likely to have bufotenine or N,N-dimethyltryptamine present in urine or elevated serum indolethylamine N-methyltransferase activity than 10 normal control subjects. The authors conclude that these are naturally occurring substances which are equally likely to be present in normal and schizophrenic subjects.


Letter: Chlorimipramine in Gilles de la Tourette's disease.


Letter: Cytarabine: therapeutic trials and editorial standards.